In medicine immunogenic compositions for administration to animals (including humans) are frequently used. Such a composition may for example be a vaccine or a diagnostic composition. Often such a composition contains an adjuvant to improve the immunological response in the animal. An important class of adjuvants, in particular in veterinairy medicine, are emulsions containing oily substances, for example emulsions of the so-called oil-in-water (O/W), water-in-oil (W/O) or water-in-oil-in-water (W/O/W) type, wherein the oily substance in general serves as the compound to boost the immunological response.
In every day practice it is advantageous that immunogenic compositions have long shelf-lives. This means that they can be stored for a long time while keeping an adequate efficacy, until needed for administration to an animal. It is generally known that antigens per se are best kept at low temperatures. However, in particular emulsions cannot be frozen without detrimental effect on their adjuvanting properties. Freezing namely can be disadvantageous for the quality of the emulsion and hence for the quality of the adjuvanting properties. Therefore, commercially available immunogenic compositions comprising adjuvanting emulsions are always accompanied with the instruction to store the composition above a freezing temperature of the emulsion. In practice, since most adjuvant emulsions are based on water, this means that the compositions are typically stored between 2 and 8° C. Although ideally suitable for maintaining an adequate emulsion quality, a temperature of between 2° C. and 8° C. means that many antigens (which often comprise complex protein or other biopolymer structures) are prone to noticable deterioration. In particular for antigens which are not too stable by nature, such as foot-and-mouth disease antigens, this means that the immunogenic properties can easily fall below an adequate level within 12 months from initial production.
In the prior art this problem has been noticed and several solutions have been found. One of these is to store the antigens separately from the adjuvant emulsion. This way, the antigens can be stored for example at a temperature of −196° C., and the emulsion at 4° C. This way, both constituents can maintain their desired properties for many years. A disadvantage of this method is that it takes some time to formulate the immunogenic composition and distribute them when needed for administration to an animal. Typically this takes 72 to 120 hours. In case of an emergency, this may be too long. Also, when there is such an emergency and the composition has to be delivered immediately after it has been formulated, the safety and potency of the composition cannot be tested.
Another solution is known from EP 1 201 251. In this patent a method is described for obtaining stratified cryogenically stored vaccines (so called SACS). This method is based on an approach of layering the individual components of a vaccine in the same primary container and then storing the product at ultra-low temperatures (around −150° C.). Although with this method a detrimental effect on potency is avoided, the method is very complex and the fact that the vaccine has to be stored at ultra-low temperatures makes the method very expensive to apply.